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CCN Investigators Present New Findings at AAIC 2014

Researchers from the Center for Cognitive Neurology (CCN), NYU School of Medicine, and the Nathan S. Kline Research Institute presented new findings at the 2014 Alzheimer's Association International Conference (AAIC) in Copenhagen, Denmark, July 12 – 17, 2014.

The Alzheimer's Association International Conference (AAIC), the world's largest forum of its kind, annually brings together researchers from around the world to report and discuss groundbreaking research and information on the cause, diagnosis, treatment and prevention of Alzheimer's disease and related disorders. Novel treatment approaches, new diagnostic and treatment-monitoring technologies, and recent findings on potentially modifiable risk factors for the disease were among the topics covered.

Focusing on discovery, progress, and change, as part of the Alzheimer's Association's research program, AAIC serves as a catalyst for generating new knowledge about dementia and fostering a vital, collegial research community. Thousands attended and more than 2,000 abstracts were presented -- all in an effort to advance the discovery of scientific breakthroughs leading to methods of prevention, treatment, and ultimately, a cure for Alzheimer's disease.

The Center for Cognitive Neurology had a strong presence at the event.

Martin J. Sadowski, MD, PhD, associate professor of neurology, psychiatry, and biochemistry and molecular pharmacology, and colleagues have identified a compound, 2-PMAP, which, in animal studies reduced by more than 50 percent levels of amyloid protein in the brain associated with Alzheimer's disease. The research was published on June 3 in Annals of Neurology.

The 2-PMAP molecule is non-toxic in mice, is easily penetrable into the brain, and lowers the production of amyloid beta and associated amyloid deposits. The prime target for Alzheimer's prevention is amyloid beta. Dr. Sadowski and colleagues screened a library of compounds and found that 2-PMAP reduced the production of amyloid beta's mother protein, known as amyloid precursor protein (APP). The APP protein normally is cut by enzymes in a way that leaves amyloid beta as one of the fragments. Dr. Sadowski's team found that 2-PMAP, even at low, non-toxic concentrations, significantly reduced APP production in test cells, lowering amyloid beta levels by 50 percent or more. The scientists subsequently found that 2-PMAP had essentially the same impact on APP and amyloid beta in the brains of living mice. The mice were engineered to have the same genetic mutations found in Alzheimer's patients with a hereditary form of the disease, causing overproduction of APP and Alzheimer's-like amyloid deposits. A five-day treatment with 2-PMAP lowered brain levels of APP and, even more so, levels of amyloid beta. Four months of treatment sharply reduced the amyloid deposits and prevented the cognitive deficits that are normally seen in these transgenic mice as they get older.

The researchers are now working to make chemical modifications to the compound to improve its effectiveness. But 2-PMAP already seems to have advantages over other amyloid-lowering compounds. One is that it can cross efficiently from the bloodstream to the brain, and thus doesn't require complex modifications that might compromise its effects on APP. The compound also appears to have a highly selective effect on APP production, by interfering with the translation of APP's gene transcript into the APP protein itself. The researchers hope that someday a treatment based on the molecule could be used to ward off the neurodegenerative disease since it may be safe enough to be taken daily over many years.

U.S. Patent No. 8,658,677 was recently issued for the 2-PMAP compound. Funding for the research was provided in part by the National Institutes of Health.

A new Core resource to support the collection, processing and management of clinical research study data is being launched by NYU Langone Medical Center (NYULMC). DataCore, based in the Medical Center IT Department and overseen by the Clinical and Translational Science Institute and its Population Health, Biomedical Informatics and Translational Library Programs will provide a range of services. Key amongst these services is the development of data management, data integrity monitoring and electronic data capture components of grants and protocols. Experience thus far has indicated that the participation of the Core in grant and protocol development will strengthen the study and increase the probability of peer-review, competitive funding. DataCore will also include capabilities that leverage the NYULMC Enterprise Data Warehouse and the use of large clinical data linked to 'omics' datasets in research. The clinical research data management goals of DataCore are to:

improve the quality of clinical research projects;

ensure the highest level of data integrity;

assist in meeting regulatory requirements for clinical research; and

enable NYULMC to become more competitive for grant and contract funding.

DataCore will make extensive use of currently available and new electronic data capture (EDC) systems and can develop clinical research study systems and registries to streamline data collection and facilitate data integrity monitoring. DataCore will also offer consultations to researchers on study development, the selection and development of EDC systems, research forms design and the use of related technologies. DataCore will also provide educational seminars, develop a forms library and assist in the development of data standards.

If requested, the DataCore team will help researchers with budget development. They will use several uniquely tailored EDC and data management options to accommodate the amount of funding clinical researchers have for specific projects. The services that DataCore plans to provide range from a do-it-yourself system that would be free of charge using NIH CTSA funded software- REDCap , to a comprehensive service which includes data management, data integrity monitoring, electronic data capture systems development and regulatory reporting.

It is envisioned that DataCore will become a long-term resource for clinical research investigators and will position NYULMC as a clinical research center with strong data management and systems development expertise. DataCore will result in an expansion of our current Data Coordinating Center that provides support for large, long-term multicenter projects.

For more information, please contact Alex Bragat or James Robinson. In order to obtain the full benefit of the Unit's expertise, it is recommended to involve DataCore as the study is being developed, rather than once it is underway.

Written by: Sloka S. Iyengar, PhD., postdoctoral fellow at the Nathan Kline Institute, New York in the lab of Dr. Helen Scharfman, James Robinson, Acting Director, DataCore at NYU Langone Medical Center, and John Speakman, Senior Director for Research IT at NYU Langone Medical Center.

In the Spotlight...

Mohammed Sheikh joined NYU Langone earlier this year and serves as a clinical trials coordinator at the Center for Cognitive Neurology. He assists with the coordination and recruitment of study subjects, is directly involved in the preparation of all IRB-related materials for new studies, engages with study investigators on enrollment ideas and completes chart reviews to determine subject eligibility. He obtained his Bachelor of Science degree from St. John's University (Jamaica, NY), with a major in Biology and double minor in Chemistry and Philosophy of Science; and earned his MD from Ross University School of Medicine (Dominica, West Indies).

What is your area of focus?
Primarily, I work with various clinical studies that focus on pharmacological and non pharmacological interventions, such as transmagnetic stimulation, to both prevent and slow down the progression of memory loss in the elderly population. There have been a number of breakthroughs in disease prevention and we are working with monoclonal antibodies, B-secretase inhibitors and intranasal insulin to name a few of our approaches to combat the disease.

What is the greatest challenge you face in your work?
In my short time working with the elderly population with memory loss I have had the privilege of meeting many people with a wide range of severity of the disease. One of the challenges in this field is sitting down with a participant and telling him/her that he/she does not meet the criteria for a particular study that he/she wanted to be a part of and was so excited to enroll in. On the bright side, we can always try to find another study that hopefully the individual is a good match for.

You have personal experience in the field of psychiatry, with knowing people who have been diagnosed with Schizophrenia. Tell us about this experience and what you believe to be your calling in life?
I took a trip to Pakistan during my third year of medical school and reconnected with an old friend I hadn't seen in years. She wasn't the same person I had met a few years prior. She was diagnosed with Schizophrenia, and I was told to stay away. She was labeled as "crazy," and shunned by the rest of her family. Inquiring into her illness and medications was a taboo. I began to think to myself, if she had proper treatment, would she have been ostracized? Is there anything else that could have been done? This inspired me to join the profession of psychiatry and help empower individuals with mental health. I want to break the taboo of treating mental illness like something that needs to be kept a secret.

You envision going back to Pakistan at some point and working with Doctors without Borders. What exactly is this program? What benefit does it provide?
Doctors without Borders was created in 1971 by a small group of French doctors with the core belief that all individuals have the right to medicine regardless of religion, race, creed or political affiliation. It is a non-governmental organization with a focus on medical-based projects in developing countries and war-torn areas. It involves a mission team comprised of various specialist physicians, nurses and medical staff who help provide services like vaccinations, medications, surgical treatments, nutrition, clean water and lastly and most importantly, psychological support.

Would you share with us your professional/personal aspirations? Where do you see yourself in 10 years?
Psychiatry is the field I belong to and fell in love with before knowing what it was. The diversity that psychiatry has to offer, its intellectual stimulation and holistic approach are a few of the reasons why I chose this field. I see myself in 10 years with a family, teaching, doing research, and raising awareness about mental illness.

What or who inspires you?
I would have to say my inspiration to become a physician came from my mother. As an obstetrician she taught me that by listening alone, she could change the treatment plans for a patient and in the long run, their well-being. It was through her ideas of individualized treatments that I learned how important it was to listen to the patient in order to understand their needs. She inspired me to combine both physical and mental health in my treatment plans.

How would a colleague describe you?
I hope my colleagues would describe me as a team player, one who they can relay upon, especially when things get messy. Also, as someone who is well organized and can plan for the future.

Funding Opportunities

Young Investigator Research Grant

The goal of the Frangione Foundation, established in 2009 by Blas Frangione, MD, PhD, Professor of Pathology and Psychiatry, is to support research on neuroscience relevant to neurodegenerative diseases.

The goal of this FOA is to establish the role of the brain innate immune system, the systemic immune system, and the crosstalk and changes with age between the two in the development and progression of Alzheimer's disease. An interdisciplinary and integrative research approach to identify the cell networks and meditators of the brain and systemic immune and inflammatory systems is expected to give greater insight into the etiological mechanisms underlying Alzheimer's disease.

In the News

Inexpensive Alzheimer's tests offer promise
USA Today- July 13th, 2014Dr. Ralph Nixon comments on new research to be presented this week at the Alzheimer's Association International Conference in Denmark, scientists show progress developing detection methods that rely on the blood, sense of smell and protein build-up in the eyes. All have been tested in dozens to hundreds of patients.

Alzheimer's blood test may predict who gets disease
CBS This Morning- July 9th, 2014Dr. James Galvin
In a new study, researchers report 87 percent accuracy in predicting who will get Alzheimer's disease within a year. Dr. James Galvin, neurologist at NYU Langone Medical Center, joins the "CBS This Morning" co-hosts to talk about the race to develop a simple test for the incurable disease.

Upcoming Events

Save the Date- ADC 25 Year Anniversary

Monday, October 27th, 2014
Alumni Hall B and Smilow Multipurpose Room

This event brings together faculty, staff and trainees from several disciplines to raise awareness of the ongoing research activities as they relate to the field of cognitive neurology and brain aging. Opening remarks will be made by Dean Robert Grossman, MD. Presentations will feature keynote guest speaker, John Trojanowski, MD, Ph.D., Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, whose research currently focuses on molecular mechanisms of neuron dysfunction, degeneration and death in normal aging and in neurodegenerative diseases. Scientific lectures will be presented by NYU investigators, followed by a comprehensive poster session and reception. Additional features of the program will be announced in a follow-up notice.

Posters will be solicted in mid August through listserv email. For more information contact Camy Sleeman atcamy.sleeman@nyumc.org.

Sunday, October 19th, Riverside Park

The Walk to End Alzheimer's is an annual event organized through the Alzheimer's Association that has raised over $300 million nationally since it began in 1989. As a friend of the Alzheimer's Association and to thank them for the support they give to patients, caregivers and researchers, the Silberstein Alzheimer's Institute will return as a sponsor for this year's event, and will host a booth.

Ways to join:
-Volunteers are needed to help represent the work being done by CCN member labs and clinics. Study coordinators are welcome to join the table to conduct recruitment.
-The CCN Team, "Aging with Excellence" is currently recruiting walkers.